Differential cone pathway influence on intrinsically photosensitive retinal ganglion cell subtypes

A small subset of ganglion cells in the mammalian retina express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). These cells are the primary conduits through which photic information is relayed to non-image-forming visual centers that mediate behaviors such as the pupillary light reflex and circadian entrainment. M1 and M2 cells comprise distinct morphological subpopulations of ipRGC, and possess physiological diversity in their intrinsic membrane properties and intrinsic light responses. Additionally, evidence now indicates that all ipRGCs receive photic information from rods/cones via synaptic signaling. It has recently been reported that Off-stratifying M1 cells paradoxically receive input from the On pathway within the Off sublamina of the inner plexiform layer. The purpose of the current study was to examine the functional consequences of cone pathway signaling to M1 and M2 cells. Using pharmacological tools and single-cell recordings of synaptic responses in wild-type and melanopsin-null mice, we found that the On pathway forms the primary excitatory synaptic input to both M1 and M2 cells. This input was much more influential in shaping the light-evoked responses and resting membrane properties of M2 cells than M1 cells. These findings indicate a surprising differential reliance upon cone-mediated phototransduction by ipRGC subpopulations. These findings also suggest that ipRGC subtypes signal diverse photic information to various non-image-forming visual centers.